Serial assessment of serum HMGB1 and ΔSOFA for predicting 28-day mortality in sepsis patients: a prospective cohort study in the emergency department

Abstract Background Prognostic assessment in sepsis involves evaluating the dynamic progression of organ dysfunction and the inflammatory response. This study compared the predictive value of serially measured serum HMGB1, a key late mediator of sepsis, with the ΔSOFA score for 28-day mortality. Methods This prospective cohort study enrolled 250 sepsis patients admitted to the emergency department of a tertiary hospital from January 2022 to August 2024. Serum HMGB1 levels and SOFA scores were dynamically assessed on Days 1, 4, and 7. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier survival analysis were utilized to compare their prognostic performance. The primary endpoint was 28-day all-cause mortality. Results A total of 232 patients (median age 71.5 years, 56.0% male) with a 28-day mortality rate of 13.8% (32/232) were included. Serum HMGB1 levels peaked on Day 4 and were significantly higher in non-survivors and septic shock patients (p < 0.05). The area under the ROC curve (AUC) for predicting 28-day mortality was 0.858 (95% CI: 0.789–0.925) for D4-HMGB1 and 0.893 (95% CI: 0.830–0.935) for D7-ΔSOFA. The AUC for D4-HMGB1 was not significantly different from that of D7-ΔSOFA (0.858 vs. 0.893, p = 0.29), but was significantly higher than that of D1-HMGB1 (0.858 vs. 0.699, p = 0.04) and D4-ΔSOFA (0.858 vs. 0.767, p = 0.01). The AUC was enhanced when HMGB1 was combined with SOFA scores, with the combination yielding higher AUC values (D7-HMGB1 + D7-SOFA: AUC = 0.898, 95% CI: 0.829–0.977, p = 0.09; D4-HMGB1 + D4-SOFA: AUC = 0.877, 95% CI: 0.792–0.928, p = 0.90) compared to the individual components at respective time points, but these increases were not statistically significant. The optimal cut-off value for D4-HMGB1 was 6.4 ng/mL. Kaplan-Meier analysis showed that patients with D4-HMGB1 ≥ 6.4 ng/mL had significantly higher mortality (log-rank test, p = 0.001). This prognostic performance remained consistent across key patient subgroups, including those with acute kidney injury, autoimmune diseases, or respiratory comorbidities. Conclusion Dynamic monitoring of serum HMGB1 levels in sepsis patients for 28-day mortality provides potential prognostic information. Specifically, D4-HMGB1 levels showed similar predictive performance for 28-day mortality to the D7-ΔSOFA score, highlighting its potential as an earlier warning tool in the emergency department. Clinical trial number Not applicable.